Device and method for resizing adipose tissue for implantation

ABSTRACT

A deagglomerator for use in resizing masses of cells is disclosed. The deagglomerator may include a plurality of apertures defined by a plurality of front and back edges. The masses of cells may be passed through the plurality of apertures from the front to the back, and from the back to the front, repeatedly. The deagglomerator may also include a plurality of blades that may aid in the deagglomeration of the cell masses. The deagglomerator may be configured between two syringes so that the tissue may be passed back and forth from the first syringe through the device to the second syringe, and then back again from the second syringe through the device and to the first syringe. In this way, the masses of cells may be properly deagglomerated.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. Provisional 62/702,614, filedJul. 24, 2018, which is hereby incorporated by reference in itsentirety.

FIELD

The invention relates to devices, systems and methods of resizing massesof tissue, including the resizing of adipose cell clusters for medicalimplantation procedures.

BACKGROUND

The following description of the background of the invention is providedsimply as an aid in understanding the invention and is not admitted todescribe or constitute prior art to the invention.

Fat cells are ideal dermal filler that can be obtained by means of aliposuction procedure which involves extraction of adipose tissue fromany donor area of the patient including, for example, subcutaneous hip,abdomen or knee areas, under local anesthesia or generally in outpatientsettings. The harvested tissue then may be reinjected into another partof the patient's body (e.g., into the patient's lips, facial wrinkles,etc.). The injected tissue may then enhance the patient's facialfullness, fill creases and/or build up shallow contours. However, uponinitial removal from the patient's body, the adipose tissue may includeagglomerated clumps of fat cells that may be too large to be reinjectedinto the patient. For example, the extracted masses of fat cells may betoo large to pass through minimally-invasive thin needles that may berequired for certain medical procedures. In addition, larger sized fatcell clusters upon injection into the patient may not interact with thepatient's stem cells as well as smaller sized fat cell clusters.

A broadly accepted method for harvesting adipose tissue for transfer isusing the negative pressure syringe technique which involves preparingthe area with tumescent solution then using a harvesting cannulaattached to 10, 30, or 60 ml syringe. The plunger is pulled back(withdrawn) to create negative pressure when the harvesting cannula ispresent at the harvesting site within the patient. The cannula is movedwithin the harvesting site until negative pressure is lost or thesyringe is full of lipoaspirate. This aspirate is then either drainedexcess fluid by either a filter, gravity separation, or centrifugationprior to the being transplanted into the patient.

The Coleman lipostructure technique is a method for processing theaspirate prior to transplantation. The harvesting syringes containingthe lipoaspirate are closed at the bottom by a Luer-lock cap and arecentrifuged to separate the liquid phase from the solid biologicalmaterial. After centrifugation, the anesthetic and biological liquidsare manually drained through the uncapped Luer-lock cap. The cellfragments and unbound oil released from lysed and damaged adipocytes areremoved only in an incomplete and rudimentary manner.

Although the Coleman and similar techniques are relatively simple andhave several advantages, they suffer certain drawbacks. First, the stepof suction and separation by centrifugation causes considerable damageand lysis of adipocytes and the concomitant release of oil. This freeoil generally is not completely removed and makes a significant portionof the lipoaspirate unusable due to high levels of oil contamination(i.e., the portion of cell material that is located on the upper part ofthe syringe barrel after centrifugation). The presence of oil in thebiological filler increases the risk of infection and rejections andcauses increased inflammation. Furthermore, these processes involvemultiple contacts of the liposuctioned material with severalinstruments, as well as a significant exposure to air in a potentiallynon-sterile environment, further increasing the risk of contaminationand, ultimately, infection.

A rarely-used technique for adipocyte processing involves mechanicalfragmentation of the suctioned cell agglomerate using a blender separatefat lobules and provide an injectable cell suspension. As with thetechniques discussed above, this blender technique suffers similardrawbacks including caused a significant amount of adipocyte damage andlysis, the potential for contamination, and that a significant portionof the harvesting material (as much as 50%) being unsuitable for use inaesthetic procedures. Furthermore, the quantity of usable cellsuspension that can be obtained using the above described procedure anddevices largely depends on the skill of the health care staff andoperational variables including the speed and operating time of theblender and centrifuge. Excessive blade speed and/or poorly maintainedcutting blades may not sufficiently separate fat lobule, but insteadcause mechanical break of the cell walls of a large amount ofadipocytes.

Other processing techniques involve washing the aspirate though a filteror strainer (fine mesh grid). This also has drawbacks. Thefilter/strainer net may become easily clogged with the harvestedmaterial which then requires a manual cleaning or removal of the fat andlarge cellular agglomerates from the mesh which also increases the riskof contamination and reduces the yield from the aspirated sample.

Accordingly, there is a need for a device, system and method that mayresize larger masses of cells (e.g., adipose cells) into smaller sizedmasses without damaging the individual cells. There is also a need to doso without unnecessarily disallowing larger masses of cells from beingresized.

SUMMARY

The present disclosure provides a device and method of use fordeagglomerating masses of cells (e.g., masses of adipose cells). Thedevice may be described as a tissue deagglomerator, a tissue sizer, or afat sizing device.

The device generally comprises a housing assembly and one or morecutting elements contained within the inner volume of that housingassembly. The housing assembly is designed to connect to a first syringeand a second syringe and create a fluid flow path therebetween. In someembodiments, the fluid flow path is substantially linear, as illustratedin the various figures. In some embodiments, the housing assemblyconnects to the syringes through ports. Optionally, the ports compriseLuer lock connectors of either the threaded or slip-fit design.

In some embodiments, the housing assembly comprises two housing members,wherein each housing member comprises a port. The housing members areadapted to be joined together either directly or through one or moreintermediate housing assembly elements such as a spacer housing, asdescribed herein. All housing assembly elements are configured toprovide a fluid-tight seal when mated. Suitable mating pair members forthe various housing assembly components include, but are not limited tothreaded connectors, snaps, notches and detents, frictional/slipfittings, and the like.

As used herein, the term “lateral” is relative and refers to thedirection towards the ports in the assembled device. Likewise, the term“medial: refers to the direction towards the center of the assembleddevice.

The one or more cutting elements may be present in any number suitablefor the desired purposed (e.g., one, two, three, four, five, six, ormore cutting elements may be present) and the cutting elements may bethe same or different, as described herein. For example, the cuttingelements may include slicers and choppers as described herein. Thecutting elements generally are configured to fit and be held firmlywithin the housing assembly. The cutting elements are generallystructured as grids or are grid-like wherein they are defined as havinga plurality of rigid members defining apertures. The apertures may beany suitable shape for the desired application and tissue type ofinterest. For example, apertures may be generally circular, oval, orovoid, triangular, square, rectangular, diamond-shaped, or any otherquadrilateral, or higher order multi-sided shape (e.g., pentagonal,hexagonal, etc.). The cutting elements are arranged perpendicular to thefluid flow path such that the apertures are in-line with the fluid flowpath. In other words, fluids flowing from one port to the other portalong the fluid flow path pass through the apertures.

As used herein, the term “length” when describing a cutting memberaperture is intended to generally refer to the longest dimension ofaperture. For example, for circular apertures, “length” refers to thecircumference; for triangular apertures, “length” refers to the longestvertex; for square, rectangular, or quadrilateral apertures, “length”refers to the longest diagonal (corner to corner); and the like. In someembodiments, the apertures have a length of 0.1 mm-10.0 mm.

As used herein, the term “grid” when describing a cutting element (e.g.,a chopper or slicer) does merely refers to a regular or irregular arrayof apertures and does not necessarily imply that the apertures aresquare or rectangular in shape. For example, FIG. 14 illustrates achopper having apertures arrayed in a “spider grid” pattern.

The cutting element members (e.g., the chopper members and the slicermembers) are the internal support members that define the apertures. Thecutting element members have at least one cutting edge on the frontside, the back side, or both. The cutting edges face the direction offluid flow such that any aggregates of cells or other particulate mattertraveling along the fluid flow path from one port to the other portencounter the cutting edge before flowing through the apertures.

As discussed herein, the device is used to size tissue (e.g., adiposetissue) aspirates prior to implantation. Typically, the tissue isharvested from the donor using a collection (first) syringe according tostandard methods. The harvested tissue is then passed from thecollection (first) syringe into a second syringe through the device once(i.e., in one direction) or back-and-forth one, two, three, four, five,six, or more times. In preferred embodiments, the tissue sample ispassed from the first syringe to the second syringe and back to thefirst syringe at least once.

In one aspect, the device comprises only a single cutting element. Thiscutting element may conform generally to the specifications of a chopperor a slicer as described herein and have aperture lengths of 0.1 mm-10.0mm. The cutting element members may have a cutting edge on one or bothfaces. It is preferable that the cutting element members have cuttingedges on both faces such that the tissue is effectively deagglomeratedwhen transferred between the syringes in both directions.

In another aspect, the device comprises two cutting elements andoptionally contains an O-ring between the cutting elements. The O-ringmay be a separate element or be integrated into one or both of thecutting elements. In some embodiments, the two cutting elements areidentical. In some embodiments the cutting element members have cuttingedges on only one face, wherein the cutting faces are lateral-facing(i.e., the non-cutting faces of the two cutting elements are medialfacing and placed “back-to-back”). In other embodiments, both sides ofthe cutting elements have cutting edges on the cutting element members.

In another aspect, the device comprises three cutting elements andoptional contains integrated or separate O-ring(s) between one or moreof the cutting elements. In one embodiment, the first and third cuttingelements are laterally-disposed and the second cutting element ismedially-disposed (i.e., sandwiched between the first and third cuttingelements), wherein the first and third cutting elements have largerapertures than the second cutting element. Optionally, the first andthird cutting elements are substantially identical. In some embodiments,the first and third cutting elements having cutting edges only on thelateral-facing surface. In other embodiments, the first and thirdcutting elements have cutting edges on both the lateral-facing andmedial-facing surface and/or optionally conform to the description of achopper as described herein. In other embodiments, the second cuttingelement has cutting edges on both faces and/or optionally conform to thedescription of a slicer as described herein.

In another aspect, the device comprises four cutting elements andoptionally contains integrated or separate O-ring(s) between one or moreof the cutting elements. In one embodiment, the first and fourth cuttingelements are laterally-disposed and the second and third cuttingelements are medially-disposed (i.e., sandwiched between the first andfourth cutting elements), wherein the first and fourth cutting elementshave larger apertures than the second and third cutting elements. Insome embodiments, the first and fourth cutting elements aresubstantially identical and/or optionally conform to the description ofa chopper as described herein. In some embodiments, the second and thirdcutting elements are substantially identical and/or optionally conformto the description of a slicer as described herein. In some embodiments,the first and fourth cutting elements having cutting edges only on thelateral-facing surfaces. In other embodiments, the first and fourthcutting elements have cutting edges on both the lateral-facing andmedial-facing surfaces. In some embodiments, the second and thirdcutting elements having cutting edges on both the lateral-facing andmedial-facing surfaces.

In other aspects, the device comprises two, three, four, five, six,seven, eight or more cutting elements, as described herein. All cuttingelements may be identical or may be different. It is generally preferredthat the cutting elements are arranged such that the configurations andcutting surfaces are symmetrical whether the device is used in the“forward” or “backward” direction. Furthermore, it is generallypreferred that, if all cutting elements are not identical, the aperturesize generally decreases in the lateral to medial direction. Forexample, if an odd number of cutting elements is used, the cuttingelements are arranged in a symmetrical pattern such as 1-2-3-2-1,wherein cutting elements 1 have the largest aperture size whichprogressively decreases to cutting element 3. Likewise, if an evennumber of cutting elements is used, the cutting elements may be arrangedin a symmetrical pattern such as 1-2-3-3-2-1.

In some embodiments of the foregoing aspects, the invention provides akit comprising two housing members, one or more spacer housings ofvariable sizes, and a plurality of cutting elements. The housingassembly members are adapted to accept a variable number of cuttingelements which may be selected and sequenced by the user. For example,the system may provide housing members which, when mated, hold a singlecutting element within the inner volume, and further provide one or morespacer housings in which may be used individually or in series toincrease the number of cutting members that can be retained within thehousing assembly. Similarly, the plurality of cutting elements may beidentical, have varying aperture size, or a combination of both in orderto provide the most flexibility to the user in configuring the device.

Other aspects and embodiments of the present invention are understoodwith reference to the figures and following description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the tissue deagglomerator device in useand attached to two syringes.

FIG. 2 is disassembled view of the tissue deagglomerator device and thetwo syringes as illustrated in FIG. 1 .

FIG. 3 is an exploded view of one configuration of the tissuedeagglomerator device of the present invention.

FIG. 4 is a perspective view of a slicer as may be used in thedeagglomeration assembly.

FIG. 5 is a schematic cross-sectional view of the unassembled deviceshown in FIG. 3 .

FIG. 6 is a schematic cross-sectional view of the assembled device shownin FIG. 3 .

FIG. 7 is a schematic cross-sectional view of a slicer, as illustratedin FIG. 6 .

FIG. 8 is a perspective view of another configuration of an assembledtissue deagglomerator device that includes a spacer housing.

FIG. 9 is an exploded view of the tissue deagglomerator deviceillustrated in FIG. 8 .

FIG. 10 is a schematic cross-sectional view of the assembled deviceshown in FIG. 8 .

FIG. 11 is a perspective view of another configuration of an assembledtissue deagglomerator device having an alternate housing member design.

FIG. 12 is an exploded view of the tissue deagglomerator deviceillustrated in FIG. 11 .

FIG. 13 is a perspective side-view of a chopper.

FIG. 14 is a schematic plan view of a front side of a chopper.

FIG. 15 is a schematic plan view of a back side of a chopper.

FIG. 16 is a cross-sectional plan view of the device shown in FIGS.11-12 .

FIG. 17 is a cross-sectional plan view of the device shown in FIGS.11-12 .

DETAILED DESCRIPTION OF THE DISCLOSURE

The invention provides a tissue homogenizer that is adapted todeagglomerate tissue samples by breaking down relatively large cellclusters into smaller clusters and/or individual cells withoutsignificantly damaging the cells. The inventive devices have particularutility for processing adipose tissue for homologous transplantation incosmetic procedures. In these procedures, it is common for the adiposetissue to be removed from one area of the patient (e.g., thesubcutaneous hip area or abdomen) and injected into another area (e.g.,the lips, facial wrinkles, etc.) for cosmetic benefit and whereinimproved outcomes may be achieved by injecting/transplanting a smoothertissue product having smaller cell clusters and agglomerations. However,upon initial removal from the patient's body, the adipose tissue mayinclude agglomerated clumps of fat cells that may too large to bereinjected into the patient and/or reinjection of those agglomerationsmay not result in the desired cosmetic effect. For example, theextracted masses of fat cells may be too large to pass through minimallyinvasive thin needles that may be required for certain medicalprocedures, or the large masses may result in a lumpy appearance wheninjected subcutaneously. Additionally, smaller-sized cell aggregates mayallow better interaction of stem cells and other cells with thosepresent at the injection site. Accordingly, deagglomeration of cellclusters prior to implantation may improve both the cosmetic andtherapeutic efficacy of the procedure.

The deagglomeration procedure preferably does little or no damage to theintact cells themselves but instead merely breaks the larger cellclusters into smaller ones or even to single cells. Deagglomeration ispreferable to the filtering techniques of the prior art becausefiltering is based on the simple removal of larger cell clusters (e.g.,by size exclusion) and necessarily reduces the yield of viable cellsfrom the extraction procedure. Deagglomeration, on the other hand,retains more of the viable extracted cells.

FIG. 1 illustrates the manner of using device 10 which is helpful inunderstanding the components and relationship among the components.Device 10 is configured to provide a fluid flow path between twosyringes 1,2. Tissue 12 from the patient collected in the first syringe1 is passed through device 10 and into the second syringe 2. As thetissue passes through device 10 in forward direction A1, large cellagglomerates are deagglomerated into smaller masses of cells. The tissuemay then be passed from the second syringe 2 through device 10 in thereverse direction A2, back into the first syringe 1 in order to providefurther deagglomeration. In this way, the device may be bidirectional.This bidirectional processing may continue for 1, 2, 3, 4, 5, 6, 7, 8,9, 10 or more cycles and/or until the overall tissue sample may bedeagglomerated into masses of the desired size. The final tissuepreparation 14 may reside either in the first syringe 1, second syringe2, or may be split between the first syringe 1 and the second syringe 2,as desired by the user.

FIG. 2 shows an exploded view of the assembled device 10 in relation tothe syringes 1,2. Device 10 provides a substantially leak-free fluidflow path between the syringes 1,2 in order to form a closed system soas to prevent contact between the tissue and the outside environment andto prevent loss of tissue during processing. This may ensure that thetissue may not be contaminated or otherwise compromised during theprocedure. Syringes 1,2 may be standard medical syringes characterizedby a plunger 1 a,2 a for generating positive and negative pressureswithin the syringe barrel for dispensing and drawing fluids,respectively. Syringes 1,2 also have tips 1 b,2 b capable of forming afluid-tight seal with device 10. In some embodiments, tips 1 b,2 b onsyringes 1,2 and ports 11 a,b on device 10 are standard Luer lockconnectors. In use, it is preferred that device 10 is configured suchthat the tissue sample may be pushed between syringes 1,2 solely byapplying positive pressure to the syringe plunger initially containingthe tissue sample. However, for samples that are viscous and/or haveparticularly large cell agglomeration, it may be necessary tosimultaneously apply a negative pressure using plugger of the receivingsyringe.

Generally, device 10 comprises a housing assembly 100 which makes up theouter body and an internal deagglomeration assembly 200 which optionallycomprises various elements that together are adapted to deagglomeratetissue samples. The deagglomeration assembly optionally includedelements including, for example, one or more choppers 202, slicers 216,and O-rings 122. The deagglomeration assembly 200 including its varioussubcomponents is housed within housing assembly 100.

As used herein, chopper 202 is a deagglomeration assembly 200 elementthat has chopper members 204 defining chopper apertures 206 and whereinat least one face (or both faces) of chopper 202 have chopper members204 with a forward-facing cutting edge rather than rounded or squarededges as is typical of a standard wire or plastic mesh. Chopperapertures 206 have a longest dimension of about 0.5-10 mm but in anyevent are longer/larger than slicer apertures 226.

As used herein, slicer 222 is a deagglomeration assembly 200 elementthat has slicer members 224 defining slicer apertures 226 and wherein atleast one face (or both faces) of slicer 222 have slicer members 224with a forward-facing cutting edge rather than rounded or squared edgesas is typical of a standard wire or plastic mesh. Slicer apertures 226have a longest dimension of about 0.2-2.5 mm but in any event areshorter/smaller than chopper apertures 206.

O-rings 122 are used as spacers between adjacent chopper 202 and/orslicer 222 because it may be desirable to have a fluid space between thecutting elements. Additionally, O-rings 122 may be placed between theinner surface of housing assembly 100 elements and the outermost cuttingelement (chopper 202 or slicer 222) in order to stability alldeagglomeration assembly 200 elements within the assembled housingassembly 100.

Each of the elements is described in detail below with reference toFIGS. 3-17 .

The Housing Assembly

The outer body of device 10 comprises housing assembly 100 that enclosesand houses deagglomeration assembly 200. Housing assembly 100 mayinclude a variety of elements as described below.

In one embodiment, housing assembly 100 comprises two housing members102 a,b that form an inner volume when mated and are adapted to housedeagglomerating assembly 200 within the inner volume. Housing members102 may have any convenient shape but a circular cross-section (lookinginto the housing member interior opening 108). However, housing members102 and the housing member opening 108 also may include cross-sectionsof other shapes such as octagonal, oval shaped, square, other shapes andany combinations thereof. In preferred embodiments, housing member 102may be generally frustoconical in shape terminating the port 11 at itsapex.

As illustrated in the various figures, a frustoconical shape is usuallypreferred for housing members 102 a,b, wherein the cylindrical portionof the housing members 102 a,b are adapted to be mated and form afluid-tight seal. The conical portion of housing member 102 provides asmall void volume and transitions the fluid flow path from the narrowdiameter of port 11 to the larger diameter of the cylindrical portionwhich forms the body of device 10. Each of housing members 102 a,bfurther comprises a port 11 which is adapted to connect to tip 22 ofsyringe 20. Preferably, port 11 is a standard Luer lock mating pairmember which, in combination with the complimentary Luer lock matingpair member on a standard syringe, forms a fluid-tight seal when mated.In other embodiments, port 11 comprises Luer-Slip fittings. It isunderstood that the scope of the device 10 is not limited in any way bythe specific configuration of port 11 and/or how it is connected to tips1 b,2 b of syringe 1,2. Port 11 also may include tubing or other typesof passageways that extend from housing member 102 to the syringe tip 1b in order to provide a fluid flow path.

As noted above, housing members 102 a,b are generally symmetrical butare adapted to be mated and form a fluid-tight seal. The matingmechanism may be reversible or irreversible depending upon the specificneed and intended use. Most conveniently, housing members 102 a,b aremanufactured and/or provided as separate elements in order to permitloading and configuration of deagglomeration assembly 200 but whereindevice 10 cannot be disassembled/reassembled once housing members 102a,b are mated. In one embodiment illustrated in FIG. 3 , housing members102 a,b are mated using complimentary threaded connectors 105 a,b suchthat housing members 102 a,b may be screwed together. In anotherembodiment illustrated in FIGS. 5-6 , housing members 102 a,b are matedusing a notch and detent system 104. Alternatively, housing members 102a,b may be mated using a simple friction fit in which the body of onehousing member 102 a is designed to slide securely into the opening 108of the other housmg member 102 b.

Housing assembly 100 optionally may include spacer housing 128 asillustrated in FIGS. 9-10 . Spacer housing 128 is adapted to extend thelength of housing assembly 100 in order to provide more internal volumefor larger deagglomeration assemblies 200. Spacer housing 128 may beprovided in a variety of lengths in order to provide a modular device 10system. As discussed in more detail below, a device 10 system may bedesigned such that housing members 102 a,b alone accept a singledeagglomeration assembly 200 element (e.g., a chopper 202 or a slicer222). One or more spacer housings 128 of different lengths may beprovided and sized such that the length of the fully assembled housingassembly 100 (including housing members 102 a,b and spacer housing 128)accept additional deagglomeration assembly 200 elements. FIG. 9illustrates spacer housing 128 having threaded connectors 105 a,b, andFIG. 10 illustrates spacer housing 128 having a notch and detent system104. It is understood that the specific connection mechanism is notlimiting or limited to those illustrated here.

In another embodiment shown in FIGS. 3 & 5 , housing member 102optionally includes one or more cutting blades 112 (e.g., 1, 2, 3, 4, 5,6, 7, or more) that may be positioned on the inner surface of housingmember 102 and within the housing member interior opening 108. In oneembodiment, the cutting blades 112 generally extend longitudinallyand/or at any angle of orientation from the port 11. Cutting blades 112have at least one sharp edge and are adapted and designed to break downthe largest tissue agglomerates which may reduce clogging of the finerdeagglomeration elements such as chopper 202 and slicer 222. Optionalcutting blades 112 may be present on either one of housing members 102 aor 102 b, or both.

In some embodiments, the entire lengths of the cutting blades 112 may beaffixed to the inner surface of housing member 102 (e.g., see cuttingblade 112 a in FIG. 5 ). In other exemplary embodiments a first end of acutting blade 112 may be affixed to an inner surface of housing member102 and a second end of the cutting blade 112 may extend freely into theinterior volume and away from the surface (e.g., see cutting blade 112 bin FIG. 5 ). The cutting blades 112 may be attached to an inner surface110 using adhesive, welding, pressure fit into receiving holes,channels, other types of attachment mechanisms or methods and anycombination thereof. Alternatively, cutting blades 112 and housingmember 102 may be co-molded or otherwise formed together integrally.

In another embodiment, housing member 102 may include support posts 124that may extend from inner surface of housing member 102 to an inserteddeagglomerating assembly 200 element. Posts 124 may thereby providelateral support to the deagglomeration assembly 200. It may bepreferable that the support posts 124 abut the front and/or the back ofa chopper 202 and/or a slicer 222 (depending on the configuration asdescribed in other sections) to provide support from both sides directlyto the chopper 202 and/or the slicer 222 itself. This may help secureand hold the deagglomeration assembly 200 in place during use of thedevice 10. Any number of support posts 124 may be used on either side ofthe deagglomeration assembly 200 as required.

The housing member 102 may be about 1-5 centimeters in diameter (e.g.,about 1, 2, 3, 4, or 5 cm), but other diameters may be used. Housingassembly 100, like all components of device 10, may be formed from ofany suitable material including, for example, polystyrene,polypropylene, polyethylene, or other types of suitable materials.

Deagglomeration Assembly

Device 10 includes a deagglomeration assembly 200 enclosed in housingassembly 100. Deagglomeration assembly 200 includes one or more elementsdescribed below which may be present individually or in any combination.

Deagglomeration Assembly—Chopper 202

In some embodiments, the deagglomeration assembly 200 includes one ormore choppers 202. As shown in FIGS. 13-15 , chopper 202 is has the samegeneral cross-sectional shape as, and is adapted to fit snugly withinhousing assembly. In one embodiment, chopper 202 is a disk-shaped gridof chopping members 204 that may be arranged to define a plurality ofchopping apertures 206. In one embodiment, the chopping members 204 maybe arranged as concentric ring members 204 b with interspaced radialmembers 204 a (e.g., spokes) extending between the rings. Chopper 202may include two concentric ring members 204 b with the outermost ring204 c defining the outer rim of the chopper 202. Other numbers of rings(e.g., one, two, three or more concentric ring members) may be used.Radial members 204 a may or may not be contiguous through the concentricring members(s) 204 b. This formation of concentric rings and radialspokes may also be referred to as a spider grid. Chopping apertures 206are defined by the concentric rings 204 b and the radial members 204 a.

In another embodiment, chopping members 204 may be arranged in agrid-like formation of rows and columns that form corresponding rows andcolumns of chopping apertures 206. Chopping members 204 may beapproximately linear sections such that four chopping members 204 mayform a generally square-, rectangular-, diamond-, or otherquadrilateral-shaped chopping aperture 206 (with each chopping member204 forming a side wall of chopping aperture 206).

In some embodiments, the dimensions of chopping apertures 206 aredesigned to break the larger clusters of cells into smaller ormedium-sized clusters that may then be broken down into even smallerdesired sizes by additional elements (e.g., slicing grids 216) as willbe described in other sections. Accordingly, the area of choppingapertures 206 is less than that of slicing apertures 226. In someembodiments, the dimensions of the chopping apertures 206 are about0.5-10 mm in the longest dimension including, for example at least 0.5,1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10.0 mm or not more than1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10.0 mm.

Choppers 202 are shaped to fit snugly within the inner volume of housingmembers 102. It is understood that choppers 202 therefore have the samecross-sectional shape as housing members 102 and are sized to provide africtional fit with the inner surface 110 of housing member 102 suchthat substantially all of the tissue sample flows though choppingapertures 206 during normal use, rather than between the outer surfaceof chopper 202 and inner surface 110.

Chopper 202 may be defined as having a front face 212 and a rear face214. Front face 212 is characterized in that chopping members 204comprise a cutting edge 208. Rear face 214 may be characterized in thatchopping members 204 have a cutting edge 208 or are is substantiallyflat (i.e., lacking cutting edge 208). Chopping members 204 that havecutting edge 208 may be used when additional cutting surfaces aredesired for deagglomeration of tissue samples and/or if deagglomerationassembly 200 comprises only a single chopper 202 and/or the singlechopper 202 is the only deagglomeration element in the deagglomerationassembly 200. Chopping members 204 that are substantially flat may aidin providing a more compact design and cause less damage to theharvested cells during the deagglomeration process.

Cutting edges 208 may be sharp along the length (preferably along itsentire length) and may result from the shape formed shape of choppingmembers 204. For example, chopping members 204 may have any convenientshape that presents an acute angle at front face 212 such as triangle orother wedge. Cutting edges 208 are adapted to slice or otherwise breakup the agglomerated fat clusters that may be impressed upon the frontface 212 as the fat tissue may be forced through the chopper 202 fromits front face 212 to its back face 214. It also is preferable that thesharpness of cutting edges 208 be not too sharp so that they may notdamage the fat cells that may come into contact with them. It also ispreferable the edges 208 not be coarse so that they may not snag orotherwise prevent the adipose clusters from passing through theapertures 206. In this way, clusters of adipose cells that may be largerin size than the chopping apertures 206 may be forced through theapertures 206 from the front 212 and broken down by the slicing actionof the chopping members 204 and their corresponding sharp front edges208. The edges 208 may be sharpened as a result of the molding processor may be sharpened during a secondary sharpening procedure as required.In addition, the edges 208 may be re-sharpened at any time as necessary.

Deagglomeration Assembly—Slicer 222

The deagglomerating assembly 200 also may include one or more slicers222. As shown in FIG. 4 , slicer 222 may comprise a plurality of slicermembers 224 that may be arranged to define a plurality of correspondingslicer apertures 226. The slicer 222 may be a disk-shaped or may includeother shapes. Slicer 222 design considerations are similar to those forchopper 202 except that the slicer apertures 226 are smaller thanchopper apertures 206 and slicer members 224 have the same or smallerdimensions/thickness compared to chopper members 204. It is generallyintended that slicer 222 produces smaller cell clusters than chopper202. Optionally, slicer 222 comprises an integrated O-ring 122 on thefront/lateral side, the back/medial side, or both. O-ring 122 may beused for spacing to a secure deagglomeration assembly 200 elementssnugly within housing assembly 100.

In some embodiments, the dimensions of slicing apertures 226 aredesigned to break the smaller or medium-sized clusters of cells intoeven smaller clusters and/or even individual cells. Accordingly, thearea of slicing apertures 226 is greater than that of chopping apertures206. In some embodiments, the dimensions of the chopping apertures 206are about 0.05-2.5 mm in the longest dimension including, for example atleast 0.05, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.6,1.8, 2.0, 2.25, or 2.50 mm or not more than 0.1, 0.2, 0.3, 0.4, 0.5,0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.25, or 2.50 mm.

Slicers 222 are shaped to fit snugly within the inner volume of housingmembers 102. It is understood that slicers 222 therefore have the samecross-sectional shape as housing members 102 and are sized to provide africtional fit with the inner surface of housing member 102 such thatsubstantially all of the tissue sample flows though slicer apertures 226during normal use, rather than between the outer surface of slicer 222and inner surface of housing member 102.

In one embodiment illustrated in FIG. 4 , the slicer members 224 arearranged in a grid-like or matrix formation of rows and columns that mayform corresponding rows and columns of slicer apertures 226. In thisexample, each slicer member 224 may be a generally straight section suchthat four slicer members 224 may form a generally square-, diamond-, orother quadrilateral-shaped slicer aperture 226 (with each slicer member224 forming a side wall of the slicer aperture 226).

As illustrated in FIG. 7 , slicer 222 may be defined as having a frontface 232 and a rear face 234. Front face 232 is characterized in thatslicing members 224 comprise a cutting edge 228. Rear face 234 may becharacterized in that slicing members 224 have a cutting edge 228 or areis substantially flat (i.e., lacking cutting edge 228). Slicing members224 that have cutting edge 228 may be used when additional cuttingsurfaces are desired for deagglomeration of tissue samples and/or ifdeagglomeration assembly 200 comprises only a single slicer 222 and/orthe single slicer 222 is the only deagglomeration element in thedeagglomeration assembly 200. Slicing members 224 that are substantiallyflat may aid in providing a more compact design and cause less damage tothe harvested cells during the deagglomeration process.

Cutting edges 228 may be sharp along the length (preferably along itsentire length) and may result from the shape formed shape of slicingmembers 224. For example, slicing members 224 may have any convenientshape that presents an acute angle at front face 232 such as triangle orother wedge. Cutting edges 228 are adapted to slice or otherwise breakup the agglomerated fat clusters that may be impressed upon the frontface 232 as the fat tissue may be forced through the slicer 222 from itsfront face 232 to its back face 234. It also is preferable that thesharpness of cutting edges 228 be not too sharp so that they may notdamage the fat cells that may come into contact with them. It also ispreferable the edges 228 not be coarse so that they may not snag orotherwise prevent the adipose clusters from passing through theapertures 226. In this way, clusters of adipose cells that may be largerin size than the slicing apertures 226 may be forced through theapertures 226 from the front 232 and broken down by the slicing actionof the slicing members 224 and their corresponding sharp front edges228. The edges 228 may be sharpened as a result of the molding processor may be sharpened during a secondary sharpening procedure as required.In addition, the edges 228 may be re-sharpened at any time as necessary.

In one embodiment, the dimensions of the slicing apertures 226 may bechosen to generally correspond to the maximum desired size of there-sized adipose cell clusters that may pass through slicer 222 (eitherfrom the front 232 or from the back 234). In this way, as the masses ofagglomerated adipose cells may pass through the slicer apertures 226,the tissue masses may be generally resized to the size of the slicerapertures 226. Note that the dimensions of the slicer apertures 226 maybe smaller than the dimensions of the chopping apertures 206. Forexample, in one embodiment it may be preferable that the slicerapertures 226 each have a width of about 50 μm (this may beapproximately the size of nano-fat particles). In another embodiment itmay be preferable that the slicer apertures 226 each have a width ofabout 100 μm. In addition, depending on the medical procedure that mayultimately utilize the resized adipose cell masses, it may be preferablethat the slicing apertures 226 each have a width of about 50 μm-2000 μmor 100 μm-1500 μm. Other widths may also be used depending on theultimate purpose of the resized tissue masses, and the scope of thedevice 10 is not limited in any way by the widths of the slicerapertures 220.

When a plurality (2, 3, 4, or more) slicers 222 are present, slicingapertures 226 a of the first slicer 222 a need not match or align withthe slicing apertures 226 b of the second slicer 222 b (or anysubsequent slicer 222) in size, shape, or orientation. In fact, havingdifferent sized and shaped slicing apertures 226 on the slicers 222 mayallow for the formation of a smaller functional aperture than anyindividual aperture 226.

In one configuration, the slicing members 224 and the slicing apertures226 of the first and second slicers 222 a,b respectively may begenerally aligned. In another configuration, the second slicer 222 b isrotated about its center axis by, for example, 90° with respect to thefirst slicer 222 a. This may place the apex or junction of four slicingmembers 224 in one slicer 222 b in the center of the slicing apertures226 a in the other slicer 222 a. That is, looking through the slicingapertures 226 a of slicer 222 a, one may see a “+” (cross) formationcreated by the junction of the slicing members 224 b. It is understoodthat while this example depicts one of the slicers 222 offset by 90°,either of the slicers 222 may be offset by other angles or orientationsto create other sized combined apertures 226. Note also that if theslicing apertures 226 may be of other shapes (e.g., circular), therotational offset of one or more of the slicers 222 may result in theformation of other sized and/or shaped combined apertures 226.

Device Assemblies

In some embodiments, the device 10 may include a deagglomeratingassembly 200 enclosed within a housing assembly 100. In variousembodiments, the deagglomeration assembly 200 includes a combination ofsome or all of the elements described above.

FIGS. 3 and 5-6 illustrate one embodiment of device 10 according to thepresent invention. FIG. 3 . shows an exploded view of device 10 whichhas a first housing member 102 a, a second housing member 102, a slicer222, and two laterally-disposed O-rings 122. Housing members 102 a,b arefrustoconical in shape terminating with Luer connectors at tips 1 a,b atthe apex. Housing members 102 a,b are illustrated in FIG. 3 as beingengaged via threaded connectors 105 a,b but it is understood that theseelements may be substituted with any appropriate connector system orpair members that create a fluid-tight seal and hold deagglomerationassembly securely inside. For example, a notch and detent system isillustrated in FIGS. 5-6 . Housing members 102 a,b are furtherillustrated as having cutting blades 112. It is understood that cuttingblades 112 are optional and may be omitted. This embodiment illustratesa deagglomeration assembly 200 having a single cutting element, slicer222. It is understood that chopper 202 may be substituted for slicer222. It is preferred that, for a deagglomeration assembly 200 having asingle cutting element, that cutting element with have cutting edges onboth faces so that the device is adapted to deagglomerate the tissuesample as the tissue is pushed in both the forward and reversedirections. This embodiment illustrates the presence of two 122 andmultiple support posts 124 that are used to secure slicer 222 withinhousing assembly 100. It is understood that one or both of O-rings 122may be integrated with slicer 222 as a rim in order to achieve the samepurpose. Support posts 124 also are optional.

FIGS. 5-6 illustrate one embodiment that may be used to secure a singlecutting element deagglomeration assembly 200. In this case, the cuttingelement is shown as slicer 222. Housing members 102 a,b are mated asdescribed herein to form the housing assembly 100, and in doing so, acircumferential notch 120 (or channel) may be formed. Notch 120 has awidth that corresponds to the width of the slicer 222 such that slicer222 is received into the notch 120 and held securely therein eitheralone or in conjunction with support posts 124 and/or O-rings 122. Inthis way, the slicer 216 may be snugly secured within the mated housingmembers 102 a,b to form the device 10.

FIGS. 8-10 illustrate another configuration of device 10. In thisembodiment, housing assembly 100 comprises a first and second housingmember 102 a,b and spacer housing 128 which is sized to allow for theincorporation of a second cutting element as part of deagglomerationassembly 200. FIG. 8 shows a perspective view of assembled device 10including first and second housing member 102 a,b and spacer housing128. FIG. 9 illustrates that the elements of housing assembly 100 may beengaged via threaded connectors 105 a,b, but it is understood that otherconnector systems may be used including, for example, an notch anddetent system 104 as illustrated in FIG. 10 . FIG. 9 further illustratesanother configuration of deagglomeration assembly 200 which includes twoslicers 222 a,b and three O-rings 122 a,b,c. FIG. 10 illustrates thatthe introduction of spacer housing 128 creates notch 120 which is largerthan notch 120 in FIG. 6 , and begin adapted to accept and secure alarger deagglomeration assembly 200. Although this embodiment isillustrated with spacer housing 128 adapted to accept two cuttingelements (slicers 222 a,b), it is understood that spacer housing 128 maybe modified to accept 3, 4, 5, 6, or more cutting elements that may be amixture of slicers 222 and choppers 202.

FIGS. 11, 12, 16, and 17 illustrate another configuration of device 10.FIG. 11 shows a fully assembled device of this embodiment includinghousing assembly 100 comprises a first and second housing member 102 a,bwhich are large enough to accommodate a deagglomeration assembly 200having multiple (four, in this case) cutting elements. As shown in FIG.12 , housing members 102 a,b are engaged using a notch and detent 104a,b system. In some embodiments, this system forms an irreversibleengagement. In this embodiment, deagglomeration assembly 200 contains afirst and second chopper 202 a,b and a first and second slicer 222 a,b.Choppers 202 a,b are disposed laterally relative to slicers 222 a,b. Inone configuration, choppers 202 a,b have cutting edges 208 on the frontface 212 a,b which are lateral facing and have flat and/or non-cuttingedges on medial-facing rear face 214 a,b. In one configurationillustrated here, slicers 222 a,b have cutting edges 228 on front faces232 a,b and rear faces 234 a,b. Optionally, O-ring 122 is disposedbetween the first slicer 222 a and the second slicer 222 b in order topromote more efficient tissue deagglomeration. As discussed above,O-ring 122 may be integral to either or both of slicers 222 a,b.Optionally, although not illustrated, O-rings 122 may be placed betweeneach chopper 202 and slicer 222.

FIG. 16 shows a cross section of this embodiment in the fully-assembledconfiguration. Optionally, choppers 202 a,b have taper 210 extending inthe lateral-to-medial direction. Taper 210 tends to increase thevelocity of the tissue sample as it passes through chopper 202 so thatit is more effectively deagglomerated by slicer 222. Taper angle α maybe about 10°-60° including, for example, about 10°, 20°, 30°, 40°, 60°,and 70°.

FIG. 17 shows a cross-section view down the fluid flow path of device 10looking from one port 11 a in the direction of the other port 11 b. Thisfigure illustrates that the tissue sample first encounters chopper 204with its relatively large apertures 206, and subsequently encountersslicer 222 with its relatively small apertures 226.

The series combination of the elements 202 a, 222 a, 222 b, 202 b maypreferably fit securely within the inner volume 116 of the housingassembly 100 without gaps or openings between the circumferentialsurfaces of the elements 202 a, 222 a, 222 b, 202 b and the innersurfaces of the housing members 102 a,b. This may ensure that tissuepassing from the first port 11 a to the second port 11 b and from secondport 11 b to the first port 11 a must pass through the apertures 206 a,226 a, 226 b, 206 b.

In addition, the series combination of the elements 202 a, 222 a, 222 b,202 b may preferably be held secure from lateral movement within theinner volume 116, especially when force may be applied to the elements202 a, 222 a, 222 b, 202 b by the tissue being pushed through theelements 202 a, 222 a, 222 b, 202 b in either direction. The elements202 a, 222 a, 222 b, 202 b may be secured by fitting the elements intocircumferential notches or between detents in the inner surfaces bypressure fit, using adhesive, welding or by other attachment methods.

Methods for Use

Device 10 may be used to break down larger sized masses of tissue intosmaller sized masses, and the resulting smaller sized masses of tissuemay be used for a variety of different medical procedures.

Adipose tissue may be removed from the patient by any adequate procedure(e.g., liposuction) and may be provided into a first syringe 1. With thefirst syringe 1 containing the adipose tissue, the plunger 1 a of thesyringe 1 may be fully or partially extended. Device 10 then may beconnected to the tip 1 b of the first syringe 1 via port 11 a. Next, thetip 2 b of a second syringe 2 (preferably empty) may be connected to theother port 11 b of the device 10. It may be preferable that the plunger2 b of the second syringe 2 be fully inserted. In this way, a leak-proofseal may be formed between the first syringe 1, the device 10 and thesecond syringe 2.

Next, the plunger 1 a of the first syringe 1 may be pressed inward topush the tissue out of the tip 1 b of the syringe 1 and into the device10. As the plunger 1 a continues to move inward, the tissue may beforced through the deagglomeration assembly 200 in the direction ofarrow A1 thereby being deagglomerated by the choppers 202 a,b, theslicers 222 a,b, and the cutting blades 112 (depending on theconfiguration and the elements of the deagglomerating assembly 200 beingused).

At the same time, the plunger 2 a of the second syringe 2 may bewithdrawn to create a negative pressure thereby pulling the tissue fromthe device 10 and into the second syringe 2. This process may preferablycontinue until the plunger 1 aa may be pressed fully into the syringe 1(so that all or at least most of the tissue may be pushed out of thesyringe 1) and the plunger 2 a may be fully extended out from thesyringe 2 (so that all or at least most of the tissue may be pulled intothe syringe 2).

Next, the plunger 2 a of the second syringe 2 may be pressed inward topush the tissue out of the tip 2 b of the syringe 2 and into the device10. As the plunger 2 b continues to move inward, the tissue may beforced through the deagglomeration assembly 200 in the direction of A2thereby being deagglomerated by the choppers 202 a,b, the slicers 222a,b, and the cutting blades 112 (depending on the configuration and theelements of the deagglomerating assembly 200 being used).

At the same time, the plunger 1 a of the first syringe 1 may beextracted out of the first syringe 1 to pull the tissue from the device10 and into the first syringe 1. This process may preferably continueuntil the plunger 2 a is pressed fully into the syringe 2 (so that allor at least most of the tissue may be pushed out of the syringe 2) andthe plunger 1 a may be fully extended out from the syringe 1 (so thatall or at least most of the tissue may be pulled into the syringe 1).

This back-and-forth procedure may be repeated as many times as necessaryto successfully resize the adipose cell masses to the desired sizes.Once the tissue has been satisfactorily refined to the proper sizes, thetissue may be collected into the first syringe 1, the second syringe 2,or any combination thereof and the device 10 may be removed from thesyringes 1,2. The tissue may then be implanted into the patient asrequired by the medical procedure.

Benefits of the Device

The benefits of the device 10 are multifold, and may include, withoutlimitation, the following benefits:

First, as described in other sections, the device 10 may properlyprepare and refine adipose tissue to be of the proper size to be usedfor certain medical procedures.

Second, the deagglomerating assembly 200 of the device 10 maydeagglomerate the adipose masses without unnecessarily damaging theindividual fat cells.

Third, the deagglomerating assembly 200 of the device 10 may not filterout the larger adipose masses, but instead may break them down to thedesired sizes.

Fourth, the bi-directional functionality of the device 10 may allow forthe tissue to be run through the deagglomerating assembly 200 multipletimes to ensure that the tissue masses are properly deagglomerated. Forexample, because the adipose cell masses may be somewhat flexible andamiable, and depending on their orientation, some of the masses maysqueeze through the apertures 206, 226 during the first pass (in thedirection of arrow A1) through the device 10 without being fullydeagglomerated. Accordingly, by enabling multiple passes back-and-forththrough the device 10, the device 10 may better ensure that the tissuemasses may ultimately be oriented properly while passing through theapertures 206, 226 to be deagglomerated by the device 10.

Fifth, because it may be impossible to force all of the tissue from thefirst syringe 1 through the device 10 on the first pass (in thedirection of arrow A1) due to the fact that some tissue may remain inthe tip 1 b and/or in the left housing member 102 a of the device 10when the plunger 1 a may be fully inserted into the first syringe 1 andthe plunger 2 a may be fully extracted from the second syringe 2, sometissue may not be deagglomerated during the first pass through thedevice 10. Accordingly, upon the second pass through the device 10 (inthe direction of arrow A2), the tissue that may not have beendeagglomerated in the first pass may be repositioned (being somewhatfluid) within the syringes 1,2 and/or the device 10 so that it may beforced through the deagglomerating assembly 200 during the second pass,or possibly during ensuing passes. In this way, by enabling multiplepasses through the device 10, the device 10 may better ensure that allor at least a high percentage of the tissue will ultimately pass throughthe deagglomerating assembly 200 to be properly deagglomerated.

Sixth, the device 10 may provide a closed system so that the tissuebeing refined may not come into contact with the outside environment,thus minimizing the chances of contamination.

Those of ordinary skill in the art will appreciate and understand, uponreading this description, that embodiments hereof may provide differentand/or other advantages, and that not all embodiments or implementationsneed have all advantages.

The invention has been described broadly and generically herein. Each ofthe narrower species and subgeneric groupings falling within the genericdisclosure also form part of the methods. This includes the genericdescription of the methods with a proviso or negative limitationremoving any subject matter from the genus, regardless of whether or notthe excised material is specifically recited herein.

Other embodiments are within the following claims. In addition, wherefeatures or aspects of the methods are described in terms of Markushgroups, those skilled in the art will recognize that the invention isalso thereby described in terms of any individual member or subgroup ofmembers of the Markush group.

It is understood by a person of ordinary skill in the art, upon readingthis specification, that any of the aspects, elements and/or details ofany of the embodiments described herein or otherwise may be combined inany way, and that the scope of the invention includes any combinationsof any aspects, elements or details of any of the embodiments hereof.

While the invention has been described in connection with what ispresently considered to be the most practical and preferred embodiments,it is to be understood that the invention is not to be limited to thedisclosed embodiment, but on the contrary, is intended to cover variousmodifications and equivalent arrangements included within the spirit andscope of the appended claims.

1. A device comprising: (a) a housing assembly defining an inner volume,the housing assembly comprising a first port, a second port, anddefining a fluid flow path there between, wherein the first port andsecond port are adapted to connect to a first syringe and a secondsyringe, respectively; (b) a cutting element disposed within the innervolume and substantially perpendicular to the flow path, wherein thecutting element comprises a plurality of rigid members defining aplurality of apertures, wherein the rigid members comprise a cuttingedge on at least one face and wherein the apertures are 0.05 mm-10 mm inlength.
 2. A method of deagglomerating tissue prior to implantation ofthe tissue in a subject comprising: (a) connecting a first syringecomprising tissue harvested from the subject to a first port of ahousing assembly of a deagglomeration device, wherein the housingassembly defines an inner volume and comprises the first port and asecond port and defines a fluid flow path there between; (b) connectinga second syringe to the second port of the housing assembly of thedeagglomeration device; (c) passing the tissue from the first syringe tothe second syringe through the inner volume of the deagglomerationdevice, wherein the inner volume comprises a cutting element disposedsubstantially perpendicular to the fluid flow path, wherein the cuttingelement comprises a plurality of rigid members defining a plurality ofapertures, and wherein the rigid members comprise a cutting edge on atleast one face; and (d) collecting the tissue from the second syringe.3. A kit comprising two housing members, one or more spacer housings ofvariable sizes, and a plurality of cutting elements, wherein the housingmembers are adapted to accept a variable number of cutting elements thatmay be selected and sequenced by a user.